Effects Of Low Concentration Of Chlorpyrifos On Cleavage Plane Orientation Of Embryonic Neuroprogenitor And The Long-term Effects Of Cell Morphology

The widely used organophosphate insecticide, chlorpyrifos (CPF) has elicited developmental neurotoxicity, and vulnerable period arrangs from the neural tube stage to nuring stage. Many studies reported the toxicity effects of CPF exposure on cell proliferation and differentiation. However, there still lacks research works on the cell division procession. The present study designed to explore the effects of CPF exposure on cleavage plane orientation and its related long-term effects on brain morphology.We administered 5mg/kg of CPF sc daily on embryonic days (E)7.5-11.5. On E12, E14 and E16, we have measured the angles at which apical progenitor cells (APs) undergo cleavage in the ventricular zone (VZ) and intermediate progenitor cells (IPs) undergo cleavage in subventricular zone (S VZ) of the developing cerebrum, we counted respectively the cells number of vertical cleavage, oblique cleavage and horizontal cleavage; In addition, the mitotic/total cells ratio was also been assessed to obtain the whole view of VZ surface. To understand the long-term effects of cells morphology, on postnatal days (PND)35, quantitative morphologic examinations were measured in CA1, CA3, and dentate gyrus regions of the hippocampus, somatosensory cortex and stritum.In the experiment, we found that most of cleavage plane orientations are vertical cleavage in the VZ, while most IPs divide with a horizontal orientation in the SVZ. After CPF treatment on E12, E14 and E16, vertical cleavage plane is deduced and obique and horizontal cleavage plane are increased; At the same time, CPF prenatal treatment donot decre ase the VZ mitotic cells number; Furthermore, CPF donot affect the cleavage plane orientation of the IPs in the SVZ at E14 and E16. At all three neurogenesis stages, we observed cleavage orientation shift from vertical to horizontal, implied the effects of CPF to switch the mode of division from symmetric division to asymmetric division, for horizontal orientation is the clear evidence of asymmetric division. The ratio of mitotic cells/total cells was found unchange in VZ surface during whole neurogenesis, which proved the orientation shift not caused by mitotic decreasing.The results of CPF prenatal exposure on PND35, selective morphology impairments were observed. In the hippocampus, showing 22.3%,2566% thinning of the CA1 and CA3 layers. The dentate guys is enlarged 24.14%. In the somatosensory cortex, the ratio of glial/neuron is increased from 22.41% to 34.23%. In the striatum, CPF elicited the neuron/total cellular number ratio with fell off 10.13%. Even without obviously system toxicity, subtoxic dosage of CPF prenatal exposure could cause slight impairments of structure on the brain of the offsprings.